Detection and management of drug-resistant tuberculosis in HIV-infected patients in lower-income countries.

SETTING: Drug resistance threatens tuberculosis (TB) control, particularly among human immunodeficiency virus (HIV) infected persons. OBJECTIVE: To describe practices in the prevention and management of drug-resistant TB under antiretroviral therapy (ART) programs in lower-income countries. DESIGN: We used online questionnaires to collect program-level data on 47 ART programs in Southern Africa (n = 14), East Africa (n = 8), West Africa (n = 7), Central Africa (n = 5), Latin America (n = 7) and the Asia-Pacific (n = 6 programs) in 2012. Patient-level data were collected on 1002 adult TB patients seen at 40 of the participating ART programs. RESULTS: Phenotypic drug susceptibility testing (DST) was available in 36 (77%) ART programs, but was only used for 22% of all TB patients. Molecular DST was available in 33 (70%) programs and was used in 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the entire course of treatment, 16 (34%) during the intensive phase only, and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line anti-tuberculosis regimens; 18 (38%) reported TB drug shortages. CONCLUSIONS: Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower-income countries. DOT was not always implemented and drug supplies were regularly interrupted, which may contribute to the global emergence of drug resistance.

Changes in antibiotic usage and susceptibility in nosocomial Enterobacteriaceae and Pseudomonas isolates following the introduction of ertapenem to hospital formulary.

There is concern that widespread usage of ertapenem may promote cross-resistance to other carbapenems. To analyse the impact that adding ertapenem to our hospital formulary had on usage of other broad-spectrum agents and on susceptibilities of nosocomial Enterobacteriaceae and Pseudomonas isolates, we performed interrupted time-series analyses to determine the change in linear trend in antibiotic usage and change in mean proportion and linear trend of susceptibility pre- (March 2004-June 2005) and post- (July 2005-December 2008) ertapenem introduction. Usage of piperacillin-tazobactam (P=0·0013) and ampicillin-sulbactam (P=0·035) declined post-ertapenem introduction. For Enterobacteriaceae, the mean proportion susceptible to ciprofloxacin (P=0·016) and piperacillin-tazobactam (P=0·038) increased, while the linear trend in susceptibility significantly increased for cefepime (P=0·012) but declined for ceftriaxone (P=0·0032). For Pseudomonas, the mean proportion susceptible to cefepime (P=0·011) and piperacillin-tazobactam (P=0·028) increased, as did the linear trend in susceptibility to ciprofloxacin (P=0·028). Notably, no significant changes in carbapenem susceptibility were observed.

Prioritising prevention strategies for patients in antiretroviral treatment programmes in resource-limited settings.

Expanded access to antiretroviral therapy (ART) offers opportunities to strengthen HIV prevention in resource-limited settings. We invited 27 ART programmes from urban settings in Africa, Asia and South America to participate in a survey, with the aim to examine what preventive services had been integrated in ART programmes. Twenty-two programmes participated; eight (36%) from South Africa, two from Brazil, two from Zambia and one each from Argentina, India, Thailand, Botswana, Ivory Coast, Malawi, Morocco, Uganda and Zimbabwe and one occupational programme of a brewery company included five countries (Nigeria, Republic of Congo, Democratic Republic of Congo, Rwanda and Burundi). Twenty-one sites (96%) provided health education and social support, and 18 (82%) provided HIV testing and counselling. All sites encouraged disclosure of HIV infection to spouses and partners, but only 11 (50%) had a protocol for partner notification. Twenty-one sites (96%) supplied male condoms, seven (32%) female condoms and 20 (91%) provided prophylactic ART for the prevention of mother-to child transmission. Seven sites (33%) regularly screened for sexually transmitted infections (STI). Twelve sites (55%) were involved in activities aimed at women or adolescents, and 10 sites (46%) in activities aimed at serodiscordant couples. Stigma and discrimination, gender roles and funding constraints were perceived as the main obstacles to effective prevention in ART programmes. We conclude that preventive services in ART programmes in lower income countries focus on health education and the provision of social support and male condoms. Strategies that might be equally or more important in this setting, including partner notification, prompt diagnosis and treatment of STI and reduction of stigma in the community, have not been implemented widely.

Dental health and viridans streptococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients.

Viridans streptococci were the most common cause of bacteremia in 61 consecutive myeloablative allogeneic hematopoietic stem cell transplant (HSCT) recipients, occurring in 19 of 31 bacteremic patients (61%) during the period of post-transplant neutropenia. Seven of the 19 had more than one viridans streptococcus in the same blood culture. Twenty isolates from 15 patients were Streptococcus mitis. Most viridans streptococci were resistant to norfloxacin, used routinely for prophylaxis. Comparison of the 19 patients with viridans streptococcal bacteremia with a contemporaneous group of 23 allogeneic HSCT recipients with fever and neutropenia but no identified focus of infection found that patients with viridans streptococcal bacteremia were more likely to have severe intraoral pathology while neutropenic (26% vs 0%) and slightly shorter interval between the last dental procedure and the onset of neutropenia (11 vs 14 days). Poor underlying dental health and the use of norfloxacin thus appear to predispose to viridans streptococcal bacteremia.

Construct stiffness of different fixation methods for supracondylar femoral fractures above total knee prostheses.

Supracondylar fracture of the femur after total knee arthroplasty has an estimated frequency of 0.6%-2.5% among total knee recipients and presents an extremely difficult problem when encountered. The goal of this study is to determine the most stable method of fixation of these supracondylar fractures among currently available devices. Synthetic composite femurs with properties similar to human bone were used, and identical, unstable supracondylar fractures were created in each. Osteotomized specimens were placed into four groups of five. Each group was then tested with one of four devices: the Green-Seligson-Henry (GSH) intramedullary nail, AO 95 degrees blade plate, dynamic condylar screw and sideplate, and condylar buttress plate. After stabilization with the different types of fixation, the constructs were tested individually for bending stiffness in four modes: flexion, extension, varus, and valgus bending. The stiffest fixation was determined in each of the four bending planes. Resistance to all tested directions was greatest for the condylar screw and sideplate construct. Resistance to flexion (stiffness = 30.96 N/mm), extension (stiffness = 36.36 N/mm), varus (stiffness = 35.46 N/mm), and valgus forces (stiffness = 32.26 N/mm) was highest in the group fixed with the dynamic condylar screw. This may be due to the purchase gained by the large lag screw into the distal femur, or it may be the result of the total rigidity of the implant. Although the femoral samples used in this study do not duplicate the typical osteopenic bone encountered at the site of a total knee arthroplasty, they do allow direct comparison of the fixation devices by removing the variability associated with cadaveric bone samples.

Negative pressure intrusion cementing technique for total knee arthroplasty.

Negative pressure intrusion (NPI) is an alternative cementing technique for the tibial baseplate of total knee arthroplasty that uses a suction cannula in the proximal tibia to remove excess fluids and fat before cementing. This technique was compared with standard third-generation positive pressure intrusion (PPI) techniques in an in vitro implantation and analysis of 6 pairs of cadaveric tibiae. Six matched pairs of fresh frozen tibiae were prepared by cutting the tibial surfaces, standard cleaning and surface drying, then performing PPI and NPI on 1 of each pair. No objective differences were noted on radiographs or direct cement depth measurement analysis. Scanning electron micrograph evaluation revealed that the PPI specimens had consistently more voids in the cement-bone composite, and the NPI specimens had consistently narrower empty spaces between bone and cement, resulting in tighter fill in NPI specimens. NPI was shown to enhance characteristics known to improve tensile and shear strength in cement-bone composites.

Detection of Chlamydia trachomatis infection in endocervical specimens using direct immunofluorescence.

A monoclonal antibody specific for Chlamydia trachomatis (Syva MicroTrak) was used to stain endocervical smears from three groups of women. When compared with results from tissue culture, direct specimen results showed 100% (15 of 15) sensitivity and 95% (164 of 172) specificity. The eight specimens with MicroTrak-positive/culture-negative results were probably true positives. Because the direct specimen test method takes less than an hour to complete, is easy to read with a fluorescence microscope, and is much less expensive than culture methods, it could become the rapid screening tool that is urgently needed in young, sexually active women.

Serum ferritin and bone marrow iron in patients undergoing continuous ambulatory peritoneal dialysis.

In 20 patients undergoing continuous ambulatory peritoneal dialysis (CAPD), serum ferritin concentration (radioimmunoassay) was compared with bone marrow iron stores (graded semiquantitatively). A close correlation between the two parameters was found. Patients with decreased iron stores (8/20) had serum ferritin concentrations below 70 ng/mL; those with normal or increased iron stores had concentrations above 96 ng/mL. It is concluded that serum ferritin concentrations adequately reflect bone marrow iron stores and are useful as a guide to iron-replacement therapy in patients undergoing CAPD.

Detection and prevalence of IUD-associated Actinomyces colonization and related morbidity. A prospective study of 69,925 cervical smears.

Cervical Papanicolaou smears from 69,925 women were screened prospectively for the presence of Actinomyces israelii. The organism was not identified in non-intrauterine (contraceptive) device (IUD)-wearers. The prevalence of A israelii among IUD wearers ranged from 1.6% (general population) to 5.3% (clinic population). Protracted IUD use seemed to predispose to a higher incidence of infection. Direct immunofluorescence proved to be a more accurate and specific method of identification when compared with conventional light microscopy and anaerobic culture. Two of 112 women with direct immunofluorescence-proved A israelii had significant clinical infections. It appears that in the vast majority of cases, IUD-associated Actinomyces colonization produces only a superficial infestation. Conservative management is suggested for asymptomatic patients with cytologically detected Actinomyces to include removal of the IUD and repeated Papanicolaou smear after the next menstrual period.

PIP: Cervical Papanicolaou smears from a population of 69,700 women including 6450 IUD users were prospectively analyzed for the presence of Actinomyces israelii during a 20-month period. No clinical evidence of actinomycete-like organisms was found in any non-IUD wearers. In IUD users, 212 Papanicolaou stained smears or 1.6% were found positive with actinomycetes when examined by light microscopy. The length of time of IUD insertion averaged 6.1 years, with a range from 6 months to 14 years. A 2nd study of 225 family planning clinic patients revealed a 5.3% prevalence of Actinomyces israelii among IUD users. Average length of IUD use was 6.5 years, with a range of 1-14 years. Direct immunofluorescence appeared more accurate for diagnosis than light microscopy or Pap smears. The study suggests that protracted IUD use predisposes to a higher incidence of infection. No specific type of IUD was associated with higher risk. Only 2 patients had clinically significant infection and most were asymptomatic, suggesting that the organism causes a superficial infestation of the endometrium which is shed with the menstrual period. Full diagnostic workup with appropriate therapy is required for the management of clinically proven infection, while asymptomatic women with cytological evidence of Actinomyces may require conservative management, including IUD removal and repeated Pap smears.

Immunomodulating properties of dimethylglycine in humans.

Dimethylglycine (DMG), a tertiary amino acid, has had wide acceptance as a nonfuel nutrient; presumably it enhances oxygen utilization by tissue and complexes free radicals. Its potential as an immunoadjuvant has also been suggested by a study of an analog of DMG, calcium pangamate. A double-blind study in 20 human volunteers showed a fourfold increase in antibody response to pneumococcal vaccine in those receiving DMG orally as compared with controls (P less than 0.01). Production of leukocyte inhibitory factor in response to concanavalin A was similar in the two groups, but those taking DMG tablets had a significantly highr mean response of leukocyte inhibition factor to streptokinase-streptodornase (P less than 0.001). The in vitro responses of lymphocytes from patients with diabetes and those with sickle cell disease to phytohemagglutinin, convanavalin A, and pokeweed mitogen were increased almost threefold after addition of DMA. These results suggest that DMG enhances both humoral and cell-mediated immune responses in humans.

T mycoplasma in human reproductive failure.

In a study of 50 women of child-bearing age, half of whom had infertility problems, it was demonstrated that the infertile group more commonly yielded Ureaplasma urealyticum on culture (84% versus 60%), had more than twice the recoveries from the endocervical canal than fertile women had (80% verse 36%), and grew a much higher log number of T mycoplasma from this locus. No particular serotype predominated as an isolate from infertile women in this study, although antisera to serotype 3 inhibited growth of most of the T mycoplasma recovered. Strains insensitive to erythromycin were recoverable from more than half of the fertile women. Of 143 patients without fertility problems there was no significant difference in Ureaplasma isolation between women who used an intrauterine device (IUD) and those who did not.

Evaluation of the humoral immune response of children with low lead exposure.

Twelve lead-exposed children, with evidence of metabolic impairment, and seven non-lead exposed children were examined for evidence of impairment of their immunological response. There were no differences between the control group and the lead exposed group with reference to complement levels, immunoglobulins, or anamnestic response to the tetanus toxoid antigen. It remains to be demonstrated whether or not there is deficient response to primary immunization, whether other antigens are more affected by lead, or whether impairment of humoral immune response requires a more serious degree of lead intoxication.

Evaluation of four methods for separation of lymphocytes from normal individuals and patients with cancer and tuberculosis.

An optimal technique was sought for lymphocyte recovery from normal and chronic diseased individuals. Lymphocytes were separated by four techniques: Plasmagel, Ficoll--Hypaque, a commercial semiautomatic method, and simple centrifugation using blood drawn from ten normal individuals, ten cancer patients, and ten tuberculosis patients. The lymphocyte mixture obtained after using each method was analyzed for percent recovery, amount if contamination by erythrocytes and neutrophils, and percent viability. The results show that the semiautomatic method yielded the best percent recovery of lymphocytes for normal individuals, while the simple centrifugation method contributed the highest percent recovery for cancer and tuberculosis patients. The Ficoll-Hypaque method gave the lowest erythrocyte contamination for all three types of individuals tested, while the Plasmagel method gave the lowest neutrophil contamination for all three types of individuals. The simple centrifugation method yielded all viable lymphocytes and thus gave the highest percent viability.